Treatment options for HUS secondary to Escherichia coli O157:H7

Shiga toxin (Stx)-producing Escherichia coli (STEC)-induced enteropathic HUS (eHUS) is a major cause of acute kidney injury in children and substantial morbidity and mortality in elderly patients. Systemic intestinal absorption of Stx and rapid uptake, through its glycolipid receptor (Gb3), by small vessel endothelial cells, are essential steps in the pathophysiology of STEC disease. HUS is characterized by intravascular hemolytic anemia, thrombocytopenia and acute kidney injury (AKI) that develop abruptly within a week of onset of STEC diarrhea/colitis. Subtle thrombotic changes, attributed to Stx-mediated endothelial injury, may not be limited to HUS. Current treatment of STEC disease targets gastrointestinal, hematological, vascular and renal complications. It includes isotonic volume replacement/expansion, red blood cell and platelet transfusion and, for severe AKI, hemo-or peritoneal dialysis. Plasma exchange is not indicated for eHUS. Novel strategies are being designed for disease prevention or amelioration, including STEC-component vaccines (Stx, protective antigens), toxin neutralizers (Stx-neutralizing monoclonal antibodies [STmAb], Gb3 mimics), and small molecules that block Stx-induced, pathogenic cellular pathways of cell activation/apoptosis. Receptor mimics and STmAb, given parenterally up to 48-72h after oro-gastric infection, protect experimental animals from otherwise lethal outcomes. Phase II/III mAb studies are planned; however, the narrow, hypothetical therapeutic window makes treatment trials challenging.